The North Central Cancer Treatment Group (NCCTG) is a multidisciplinary clinical trials organization with the Research Base headquarters located at the Mayo Clinic Cancer Center (MCCC) in Rochester, Minnesota, and membership composed largely of community oncology practices distributed throughout the United States. Since most cancer care in the United States is provided in the community, NCCTG posits that clinical cancer research, conducted in partnership with community practices, provides answers that most accurately reflect outcomes relevant to patient care. The specific aims of NCCTG are: 1) to improve the duration and quality of life of patients with cancer, 2) to improve understanding of the biology of cancer and the biological consequences of treatment, 3) to improve methods for conducting clinical trials, and 4) to provide an infrastructure for the conduct of cancer control research. These aims are carried out through the efforts of four Disease Committees: Breast Cancer, Gastrointestinal Cancer, Lung Cancer, and Neuro- oncology; three Modality Committees: Surgery, Radiation Oncology, and Pathology; three Discipline- oriented Scientific Committees: Novel Therapeutics, Quality of Life, and Cancer Control; and five Core Function Committees: Audit, Oncology Nursing Board, Clinical Research Associate Board, Cancer Health Disparities, and Patient Advocate. The research activities of these committees are supported by the Statistics and Data Center and by the Operations Center, both in partnership with the MCCC. NCCTG investigators have contributed substantially to treatment advances for cancer patients in the past grant cycle by demonstrating the superiority of oxaliplatin-based treatment regimens in advanced colorectal cancer and the combination of trastuzumab with adjuvant chemotherapy for patients with loco-regional breast cancer overexpressing the HER-2 protein. We have advanced knowledge of the treatment of patients with brain tumors, especially low-grade glioma, and genetic determinants of outcome in both low- and high-grade glioma, and have identified both successful and unsuccessful cytotoxic, targeted, and radiotherapeutic approaches in patients with breast, lung, colon, pancreatic and esophageal cancers, glioma, hepatoma, lymphoma, and melanoma. We have verified the safety and efficacy of laparoscopic. surgery for patients with colon cancer and for combined surgery and chemotherapy for patients with colorectal cancer metastatic to liver. We have identified the prognostic and predictive value of pharmacogenetic and tumor tissue genetic markers in patients with specific cancers, and have evaluated the validity of surrogate endpoints for carefully defined patient groups. Collectively, these achievements demonstrate the scientific value of NCCTG and provide evidence that NCCTG will continue to contribute meaningful scientific advances in the next grant cycle, as proposed within this grant application.